{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:48:37Z","timestamp":1765212517335,"version":"3.46.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"am","delay-in-days":297,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Structural Biology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.jsb.2025.108250","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T01:11:10Z","timestamp":1758589870000},"page":"108250","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precise ligand-selective mechanism at the fab domain of a tau-recognizing antibody"],"prefix":"10.1016","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9024-9210","authenticated-orcid":false,"given":"Tomohiro","family":"Tsuchida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Tsuchiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuhiko","family":"Minoura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0083-5847","authenticated-orcid":false,"given":"Yasuko","family":"In","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsushiro","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taizo","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshimasa","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Tomoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jsb.2025.108250_b0005","doi-asserted-by":"crossref","unstructured":"J. Weller, A. Budson (2018) Current understanding of Alzheimer's disease diagnosis and treatment. F1000Research 7, https:\/\/doi.org\/10.12688\/ f1000research.14506.1.","DOI":"10.12688\/f1000research.14506.1"},{"key":"10.1016\/j.jsb.2025.108250_b0010","unstructured":"World Health Organization (2017) Global Action Plan on the Public Health Response to Dementia. http:\/\/apps.who.int\/bookorders."},{"issue":"1","key":"10.1016\/j.jsb.2025.108250_b0015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5114\/fn.2013.34190","article-title":"Molecular mechanisms of neuropathological changes in Alzheimer\u2019s disease","volume":"51","author":"\u0160er\u00fd","year":"2013","journal-title":"Folia Neuropathol."},{"issue":"1\u20132","key":"10.1016\/j.jsb.2025.108250_b0020","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/0006-8993(92)91092-S","article-title":"Alzheimer neurofibrillary tangles contain 2.1 nm filaments structurally identical to the microtubule-associated protein \u03c4: a high-resolution transmission electron microscope study of tangles and senile plaque core amyloid","volume":"590","author":"Ruben","year":"1992","journal-title":"Brain Res."},{"key":"10.1016\/j.jsb.2025.108250_b0025","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1073\/pnas.83.11.4040","article-title":"Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau","volume":"83","author":"Wood","year":"1986","journal-title":"Proc. Nail. Acad. Sci. USA"},{"key":"10.1016\/j.jsb.2025.108250_b0030","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1083\/jcb.118.3.573","article-title":"Alzheimer-like Paired Helical Filaments and Antiparallel Dimers formed from Microtubule-associated Protein Tau In Vitro","volume":"118","author":"Wiue","year":"1992","journal-title":"J. Cell Biol."},{"issue":"12","key":"10.1016\/j.jsb.2025.108250_b0035","doi-asserted-by":"crossref","first-page":"3856","DOI":"10.1021\/bi061359o","article-title":"Granular tau oligomers as intermediates of tau filaments","volume":"46","author":"Maeda","year":"2007","journal-title":"Biochem."},{"key":"10.1016\/j.jsb.2025.108250_b0040","doi-asserted-by":"crossref","first-page":"15712","DOI":"10.1073\/pnas.95.26.15712","article-title":"A nucleated assembly mechanism of Alzheimer paired helical filaments","volume":"95","author":"Friedhoff","year":"1998","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"1","key":"10.1016\/j.jsb.2025.108250_b0045","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade","volume":"9","author":"Jack","year":"2010","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.jsb.2025.108250_b0050","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1083\/jcb.101.4.1371","article-title":"The distribution central nervous of tau in system the mammalian central nervous system","volume":"101","author":"Binder","year":"1985","journal-title":"J. Cell Biol."},{"issue":"1","key":"10.1016\/j.jsb.2025.108250_b0055","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0306-4522(88)90013-9","article-title":"Both adult and juvenile tau microtubule-associated proteins are axon specific in the developing and adult rat cerebellum","volume":"25","author":"Brion","year":"1988","journal-title":"Neuroscience"},{"issue":"2","key":"10.1016\/j.jsb.2025.108250_b0060","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/37.2.2492045","article-title":"Distribution of tau proteins in the normal human central and peripheral nervous system","volume":"37","author":"Trojanowski","year":"1989","journal-title":"J. Histochem. Cytochem."},{"issue":"5","key":"10.1016\/j.jsb.2025.108250_b0065","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1016\/S0021-9258(18)53710-8","article-title":"Functional organization of microtubule-associated protein tau","volume":"268","author":"Brandt","year":"1993","journal-title":"J. Biol. Chem."},{"issue":"204","key":"10.1016\/j.jsb.2025.108250_b0070","article-title":"Role of tau as a microtubule-associated protein: structural and functional aspects","volume":"11","author":"Barbier","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.jsb.2025.108250_b0075","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nrn.2015.1","article-title":"Tau in physiology and pathology","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.jsb.2025.108250_b0080","first-page":"110","article-title":"Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer\u2019s disease","volume":"1502","author":"Goedert","year":"2000","journal-title":"Biochem. Biophys. Acta."},{"key":"10.1016\/j.jsb.2025.108250_b0085","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fnagi.2019.00204","article-title":"Role of tau as a microtubule-associated protein: structural and functional aspects","volume":"11","author":"Barbier","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.jsb.2025.108250_b0090","doi-asserted-by":"crossref","first-page":"5721","DOI":"10.1242\/jcs.01558","article-title":"Tau phosphorylation in neuronal cell function and dysfunction","volume":"117","author":"Johnson","year":"2004","journal-title":"J. Cell Sci."},{"issue":"1","key":"10.1016\/j.jsb.2025.108250_b0095","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3390\/biom6010006","article-title":"Tau protein hyperphosphorylation and aggregation in Alzheimer\u2019s disease and other tauopathies, and possible neuroprotective strategies","volume":"6","author":"\u0160imic","year":"2016","journal-title":"Biomolecules"},{"key":"10.1016\/j.jsb.2025.108250_b0100","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3389\/fnins.2019.01274","article-title":"Tau propagation as a diagnostic and therapeutic target for dementia: potentials and unanswered questions","volume":"13","author":"Takeda","year":"2019","journal-title":"Front. Neurosci."},{"issue":"3","key":"10.1016\/j.jsb.2025.108250_b0105","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3390\/ijms19030645","article-title":"Tau spreading mechanism implications for dysfunctional tauopathies","volume":"19","author":"Fuster-Matanzo","year":"2018","journal-title":"Mol. Sci."},{"issue":"23","key":"10.1016\/j.jsb.2025.108250_b0110","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1002\/cbic.201800288","article-title":"Transcellular spreading of tau in tauopathies","volume":"19","author":"Demaegd","year":"2018","journal-title":"Chembiochem"},{"issue":"4","key":"10.1016\/j.jsb.2025.108250_b0115","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.biopsych.2017.04.003","article-title":"Prion-like spreading in tauopathies","volume":"83","author":"Ayers","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.jsb.2025.108250_b0120","first-page":"238","article-title":"Tau and tauopathies, Brain Res","volume":"126","author":"Arendt","year":"2016","journal-title":"Bulletin of the Georgian Academy of Sciences"},{"key":"10.1016\/j.jsb.2025.108250_b0125","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/j.1460-2075.1989.tb03390.x","article-title":"Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain","volume":"8","author":"Goedert","year":"1989","journal-title":"EMBO J."},{"key":"10.1016\/j.jsb.2025.108250_b0130","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1073\/pnas.85.11.4051","article-title":"Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau","volume":"85","author":"Goedert","year":"1988","journal-title":"PNAS"},{"key":"10.1016\/j.jsb.2025.108250_b0135","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0014-5793(92)81094-3","article-title":"The microtubule binding repeats of tau protein assemble into filaments like those found in Alzheimer's disease","volume":"309","author":"Crowther","year":"1992","journal-title":"FEBS Lett."},{"key":"10.1016\/j.jsb.2025.108250_b0140","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/jb\/mvg116","article-title":"Aggregation analysis of the microtubule binding domain in tau protein by spectroscopic methods","volume":"134","author":"Yao","year":"2003","journal-title":"J. Biochem."},{"key":"10.1016\/j.jsb.2025.108250_b0145","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.bbrc.2006.02.185","article-title":"Fluorescence-coupled CD conformational monitoring of filament formation of tau microtubule-binding repeat domain","volume":"343","author":"Mizushima","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jsb.2025.108250_b0150","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/jb\/mvi142","article-title":"Possible role of each repeat structure of the microtubule-binding domain of the tau protein in in vitro aggregation","volume":"138","author":"Tomoo","year":"2005","journal-title":"J. Biochem."},{"key":"10.1016\/j.jsb.2025.108250_b0155","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/jb\/mvs061","article-title":"C-H p interplay between Ile308 and Tyr310 residues in the third repeat of microtubule binding domain is indispensable for self- assembly of three-and four-repeat tau","volume":"152","author":"Sogawa","year":"2012","journal-title":"J. Biochem."},{"key":"10.1016\/j.jsb.2025.108250_b0160","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/bip.22489","article-title":"Ch-p interaction in VQIVYK sequence elucidated by NMR spectroscopy is essential for PHF formation of tau","volume":"102","author":"Sogawa","year":"2014","journal-title":"Biopolymers"},{"key":"10.1016\/j.jsb.2025.108250_b0165","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nature05695","article-title":"Atomic structures of amyloid cross-b spines reveal varied steric zippers","volume":"447","author":"Sawaya","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.jsb.2025.108250_b0170","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1021\/ja110545h","article-title":"Macrocyclic b-sheet peptides that inhibit the aggregation of a tau-protein-derived hexapeptide","volume":"133","author":"Zheng","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.jsb.2025.108250_b0175","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-18443-2","article-title":"Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids","volume":"8","author":"KrishnaKumar","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jsb.2025.108250_b0180","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nchem.2889","article-title":"Structure-based inhibitors of tau aggregation","volume":"10","author":"Seidler","year":"2018","journal-title":"Nat. Chem."},{"key":"10.1016\/j.jsb.2025.108250_b0185","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.febslet.2005.01.039","article-title":"Effects of different anti-tau antibodies on tau fibrillogenesis: RTA-1 and RTA-2 counteract tau aggregation","volume":"579","author":"Taniguchi","year":"2005","journal-title":"FEBS Lett."},{"issue":"13","key":"10.1016\/j.jsb.2025.108250_b0190","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1002\/1873-3468.13791","article-title":"Crystal structure of the human tau PHF core domain VQIINK complexes with the Fab domain of monoclonal antibody Tau2r3","volume":"594","author":"Tsuchida","year":"2020","journal-title":"FEBS Lett."},{"key":"10.1016\/j.jsb.2025.108250_b0195","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.bbrc.2021.11.025","article-title":"Structural study of the recognition mechanism of tau antibody Tau2r3 with the key sequence (VQIINK) in tau aggregation","volume":"585","author":"Tsuchida","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"1","key":"10.1016\/j.jsb.2025.108250_b0200","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/pro.2187","article-title":"A comparison of successful and failed protein interface designs highlights the challenges of designing buried hydrogen bonds","volume":"22","author":"Stranges","year":"2013","journal-title":"Protein Sci."},{"key":"10.1016\/j.jsb.2025.108250_b0205","doi-asserted-by":"crossref","unstructured":"Simon Mitternacht (2016) FreeSASA: An open source C library for solvent accessible surface area calculation. F1000Research 5:189.","DOI":"10.12688\/f1000research.7931.1"},{"issue":"8","key":"10.1016\/j.jsb.2025.108250_b0210","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/335188a0","article-title":"Elbow motion in the immunoglobulins involves a molecular ball-and-socket joint","volume":"335","author":"Lesk","year":"1988","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.jsb.2025.108250_b0215","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jmb.2017.12.012","article-title":"Locking the Elbow: improved Antibody Fab Fragments as Chaperones for Structure Determination","volume":"430","author":"Bailey","year":"2017","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jsb.2025.108250_b0220","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature23002","article-title":"Cryo-EM structures of tau filaments from Alzheimer's disease","volume":"547","author":"Fitzpatrick","year":"2017","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.jsb.2025.108250_b0225","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0038903","article-title":"Fibril-Forming Motifs Are Essential and Sufficient for the Fibrillization of Human Tau","volume":"7","author":"Meng","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.jsb.2025.108250_b0230","doi-asserted-by":"crossref","first-page":"6471","DOI":"10.1016\/j.bmc.2014.09.032","article-title":"Phosphorylation regulates fibrillation of an aggregation core peptide in the second repeat of microtubule-binding domain of human tau","volume":"22","author":"Inoue","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.jsb.2025.108250_b0235","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1006\/jmbi.1998.1684","article-title":"Ligand-induced domain movement in an antibody Fab: molecular dynamics studies confirm the unique domain movement observed experimentally for Fab NC6.8 upon complexation and reveal its segmental flexibility","volume":"278","author":"Sotriffer","year":"1998","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jsb.2025.108250_b0240","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S0006-3495(00)76320-X","article-title":"Elbow flexibility and ligand-induced domain rearrangements in antibody Fab NC6.8: large effects of a small hapten","volume":"79","author":"Sotriffer","year":"2000","journal-title":"Biophys. J ."},{"issue":"9","key":"10.1016\/j.jsb.2025.108250_b0245","doi-asserted-by":"crossref","first-page":"6783","DOI":"10.1074\/jbc.M605197200","article-title":"Structural Consequences of Mutations in Interfacial Tyr Residues of a Protein Antigen-Antibody complex","volume":"282","author":"Shiroishi","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jsb.2025.108250_b0250","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S1074-5521(96)90164-7","article-title":"Just add water! the effect of water on the specificity of protein-ligand binding sites and its potential application to drug design","volume":"3","author":"Ladbury","year":"1996","journal-title":"Chem. Biol."},{"key":"10.1016\/j.jsb.2025.108250_b0255","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.jmb.2006.01.023","article-title":"Antibody elbow angles are influenced by their light chain class","volume":"357","author":"Stanfield","year":"2006","journal-title":"J. Mol. Biol."}],"container-title":["Journal of Structural Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1047847725000851?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1047847725000851?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:43:37Z","timestamp":1765212217000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1047847725000851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S1047847725000851"],"URL":"https:\/\/doi.org\/10.1016\/j.jsb.2025.108250","relation":{},"ISSN":["1047-8477"],"issn-type":[{"type":"print","value":"1047-8477"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Precise ligand-selective mechanism at the fab domain of a tau-recognizing antibody","name":"articletitle","label":"Article Title"},{"value":"Journal of Structural Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jsb.2025.108250","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"108250"}}